The ginormous 67th American Academy of Neurology (AAN) annual meeting is in full swing, with more than 2,500 abstracts scheduled for presentation at scientific sessions during the week. If the emerging science abstracts – formerly called the "late-breakers" – are any indication, therapeutic advances targeting Alzheimer's disease (AD) will dominate conversations at AAN, although significant updates on approaches to treat epilepsy, multiple sclerosis and Parkinson's disease also are planned.

Biogen Inc. will lead the data blitz during the first 45 minutes of the emerging science platform session Wednesday evening with an update on aducanumab (BIIB037), its human recombinant monoclonal antibody (MAb) targeting aggregated forms of beta-amyloid, including soluble oligomers and insoluble fibrils deposited into the amyloid plaque in the brains of AD patients. The Cambridge, Mass.-based company made a splash last month at the 12th International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders in Nice, France, reporting that that BIIB037 showed a dose- and time-dependent reduction of amyloid plaque in the brain in a pre-specified interim analysis of its ongoing phase Ib PRIME study. (See BioWorld Today, March 23, 2015.)

The drug was in-licensed in 2007 from Zurich, Switzerland-based Neurimmune Therapeutics AG.

Biogen already disclosed that it plans to move BIIB037 into a phase III study this year, so the AAN data are likely to be more iterative in nature. In its emerging science abstract, the company strengthened the case for its premise, showing that beta-amyloid knockdown by ApoE status was time and dose-dependent regardless of whether patients were prodromal or showed mild AD. That's not a huge revelation over what the company shared in Nice, and Biogen didn't tip its hand about additional revelations during its three minutes in the spotlight Wednesday night.

"What does it mean?" asked RBC Capital Markets analyst Michael Yee in a first glance after the AAN emerging science abstracts dropped. For starters, he answered, the drug appears to have good efficacy and amyloid knockdown, with amyloid-related imaging abnormalities (ARIA) occurring at high doses.

"Some bears think ARIA is 'unblinding' some docs, which is why high dose has great efficacy," Yee pointed out. He added, however, that the data were silent on whether physicians or nurses – who would be blinded to ARIA – conducted the memory exams or if efficacy was more directly linked to the biology of ARIA.

"We'll know more if we know cognition by APO status," Yee said. Although that information could come in Wednesday's presentation, the company "is not saying if we'll get this yet," he conceded, though more color on BIIB037 should come, either way, during the company's earnings call on Friday.

The drug candidate is part of a broad AD partnership between Biogen and Eisai Co. Ltd., of Tokyo, inked last year. (See BioWorld Today, March 6, 2014.)

"BIIB/Eisai seem to have the strongest shot on goal in the Aβ/AD race," according to Joshua Schimmer and colleagues at Piper Jaffray, which recently published an exhaustive analysis of Biogen's amyloid program, encompassing "two rationally designed monoclonal antibodies" and a beta secretase (BACE) inhibitor. "If amyloid is indeed a strong target to modify the disease course in AD, a combination of an antibody and a BACE inhibitor may make the most sense," the analysts wrote, and "few companies have that combination."

One company not out of the race – at least in early stage AD – is Eli Lilly and Co. The Indianapolis-based pharma will present an abstract about the thesis underpinning the phase III EXPEDITION3 study of its MAb, solanezumab (sola), which missed both the cognitive and functional endpoints in two earlier double-blind, placebo-controlled EXPEDITION trials in patients with mild to moderate AD but showed a silver lining: a pre-specified secondary analysis of pooled data across the first two EXPEDITION trials suggested statistically significant slowing of cognitive decline in the overall study population. (See BioWorld Today, July 13, 2013.)

Lilly researchers compared delayed- and early start treatment with sola to test the hypothesis of the drug's disease-modifying effect, concluding that patients who received sola during the double-blind studies had a cognitive benefit that was not recovered by those who began the drug in the extension trial.

"The takeaways from this work are that the method can be used to analyze delayed-start data to assess potential disease modification effect and, based on this method, the six-month data on sola demonstrated that the effect appears to be consistent with disease-modifying effects," Hong Liu-Seifert, research advisor at Lilly, told BioWorld Today.

"The findings are consistent with a treatment that doesn't just address the symptoms," added Eric Siemers, senior medical director of Lilly's AD team. "It's exciting to have an investigational treatment that does that and to actually have the statistical methodology worked out."

The Lilly presentation is scheduled for Thursday.

EPILEPSY DRUG STUDIES ALSO FRONT AND CENTER

Outside Alzheimer's, several important updates are scheduled in epilepsy treatment. An investigator-sponsored trial by researchers at the New York University (NYU) Langone Comprehensive Epilepsy Center provided additional evidence that the cannabis-derived drug, Epidiolex, from GW Pharmaceuticals plc, may show promise in treating severe forms of epilepsy that don't respond to other treatments.

The study involved 213 people, ranging from toddlers to adults, with a median age of 11 who had refractory epilepsy, including those with Dravet and Lennox-Gastaut syndromes. Findings from the open-label study suggested that, for the 137 people who completed the 12-week treatment period, the number of seizures decreased by an average of 54 percent from baseline. Among 23 people with Dravet syndrome who finished the study, the number of convulsive seizures decreased by 53 percent. The 11 people with Lennox-Gastaut syndrome who finished the study had a 55 percent reduction in the number of atonic seizures.

Both investigators and GW officials were cautiously optimistic about the findings, which will be presented Wednesday evening at the AAN meeting. Daniel Friedman, assistant professor of neurology at NYU Langone, observed that individuals with epilepsy have fluctuations in seizure activity and that the counting of seizures is "slightly subjective, so it can be prone to biases and prone to error." Nevertheless, the significant decrease in seizure activity for individuals in the study merits additional randomized, placebo-controlled study to produce scientific evidence on the case for cannabidiol (CBD) in epilepsy treatment, Friedman said.

"This study emerged out of a really striking interest within the epilepsy community in the potential effects of cannabis-derived CBD to treat epilepsy," added Justin Gover, CEO of London-based GW, emphasizing that the findings came directly from physician-led, FDA-authorized Epidiolex expanded access programs.

Still, "as the originator of the product, we at GW watched very closely and are very interested in the effect," Gover told BioWorld Today. "The data we're seeing inform us about how to best develop this product formally for FDA approval."

GW recently launched a phase III trial of Epidiolex in Dravet and has others coming this year. (See BioWorld Today, March 10, 2015.)

Sage Therapeutics Inc. also posted an emerging science abstract of phase I/II data of SAGE-547 in super-refractory status epilepticus (SRSE). Results of the study, designed to evaluate safety and tolerability, showed 71 percent, or 12 of 17 evaluable patients, were weaned off their anesthetic agents while SAGE-547 was being administered, and 71 also were successfully weaned off SAGE-547. The company concluded that the trial demonstrated activity in SRSE with a favorable safety profile and predictable exposures.

The abstract, which will be presented Wednesday evening, offered incrementally more data than findings posted late last year by the Cambridge, Mass.-based company. Earlier this month, Sage reported that it reached agreement with the FDA on a phase III protocol for a pivotal trial of SAGE-547 in SRSE. (See BioWorld Today, Nov. 11, 2014.)

With Sage continuing to enroll the phase I/II to keep sites recruiting patients and ready to move into the phase III, the development timetable could be very quick, with Leerink Partners LLC analyst Joseph Schwartz predicting in a recent note that the drug could be launched before year-end 2017.

Among the other presentations slated for the emerging science platform session are an update on Gilenya (fingolimod) in patients with primary progressive multiple sclerosis by Novartis AG, of Basel, Switzerland; use of NNZ-2566, from Neuren Pharmaceuticals Ltd., of Sydney, to treat young women with Rett syndrome; first-time use of SD-809, from Auspex Pharmaceuticals Inc., of La Jolla, Calif., in Huntington's disease; and the effect of triheptanoin, from Ultragenyx Pharmaceutical Inc., of Novato, Calif., in reducing the frequency of paroxysmal movement disorders in GLUT1 deficiency.

The AAN meeting continues through Saturday.